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Vitamin D Supplementation in Patients With Type 2 Diabetes: The Vitamin D for Established Type 2 Diabetes (DDM2) Study.

ABSTRACT: Observational data support a role for vitamin D in type 2 diabetes, but evidence from trials is inconclusive.To evaluate the effect of vitamin D supplementation on ?-cell function and hemoglobin A1c (HbA1c) in patients with well-controlled type 2 diabetes.Double-blind, randomized, placebo-controlled clinical trial.Tufts Medical Center, Boston, MA; VA Medical Center, Cincinnati, OH.A total of 127 patients (mean age, 60 years) with stable (HbA1c ?7.5%) diabetes managed with lifestyle only or lifestyle plus metformin.Subjects were given 4000 units of vitamin D3 (cholecalciferol) daily or placebo for 48 weeks.Insulin secretion rate (ISR) was estimated from peripheral plasma C-peptide levels after a 3-hour 75-g oral glucose tolerance test done at baseline and week 24. Changes in HbA1c were assessed at 16, 24, 36, and 48 weeks.Baseline mean plasma 25-hydroxyvitamin D [25(OH)D] concentration was 26.6 ng/mL, mean HbA1c was 6.6%, and 78% of patients were on metformin. At week 24, mean 25(OH)D changed by 20.5 and -1.6 ng/mL in the vitamin D and placebo groups, respectively (P < 0.001). The vitamin D and placebo groups did not differ in change in ISR or HbA1c. Among patients treated with lifestyle only (n = 28), vitamin D supplementation reduced HbA1c compared with placebo (-0.1% vs 0.3%, respectively; P = 0.034) at week 24. This result was not observed at the other time points and could be due to chance.Vitamin D3 at 4000 IU/d did not change ISR or HbA1c in patients with well-controlled type 2 diabetes on metformin not selected for vitamin D deficiency.

SUBMITTER: Angellotti E

PROVIDER: S-EPMC5848819 | biostudies-other | 2018 Apr

REPOSITORIES: biostudies-other

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Vitamin D Supplementation in Patients With Type 2 Diabetes: The Vitamin D for Established Type 2 Diabetes (DDM2) Study.

Angellotti Edith E D'Alessio David D Dawson-Hughes Bess B Nelson Jason J Cohen Robert M RM Gastaldelli Amalia A Pittas Anastassios G AG

Journal of the Endocrine Society 20180226 4

<h4>Context</h4>Observational data support a role for vitamin D in type 2 diabetes, but evidence from trials is inconclusive.<h4>Objective</h4>To evaluate the effect of vitamin D supplementation on <i>β</i>-cell function and hemoglobin A1c (HbA1c) in patients with well-controlled type 2 diabetes.<h4>Design</h4>Double-blind, randomized, placebo-controlled clinical trial.<h4>Setting</h4>Tufts Medical Center, Boston, MA; VA Medical Center, Cincinnati, OH.<h4>Participants</h4>A total of 127 patients ...[more]

PMID: 29577107

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Project description:Sphingolipids are characterized by a broad range of bioactive properties. Particularly, the development of insulin resistance, a major pathophysiological hallmark of Type 2 Diabetes mellitus (T2D), has been linked to ceramide signaling. Since vitamin D supplementation may slow down T2D progression by improving glucose concentrations and insulin sensitivity, we investigated whether vitamin D supplementation impacts on plasma sphingolipid levels in T2D patients. Thus, plasma samples of 59 patients with non-insulin-requiring T2D from a placebo-controlled, randomized, and double-blind study were retrospectively analyzed. Once per week, patients received either 20 drops of Vigantol oil, corresponding to a daily dose of 1904 IU/d vitamin D (verum: n = 31), or a placebo oil consisting of medium chain triglycerides (placebo: n = 28). Blood samples were taken from all of the participants at three different time points: 1) at the beginning of the study (baseline), 2) after 6 months supplementation, and 3) after an additional 6 months of follow-up. Plasma sphingolipids were measured by high-performance liquid chromatography tandem mass spectrometry. At baseline and 6 months follow-up, no significant differences in plasma sphingolipid species were detected between the placebo and verum groups. After 6 months, vitamin D supplementation significantly enhanced plasma C18dihydroceramide (dhCer; N-stearoyl-sphinganine (d18:0/18:0)) and C18ceramide (Cer; N-stearoyl-sphingosine (d18:1/18:0)) levels were observed in the verum group compared to the placebo group. This was accompanied by significantly higher 25-hydroxyvitamin D? (25(OH)D?) blood levels in patients receiving vitamin D compared to the placebo group. Taken together, vitamin D supplementation induced changes of the C18 chain-length-specific dhCer and Cer plasma levels in patients with T2D. The regulation of sphingolipid signaling by vitamin D may thus unravel a novel mechanism by which vitamin D can influence glucose utilization and insulin action. Whether this acts favorably or unfavorably for the progression of T2D needs to be clarified.

Dataset Information

Vitamin D Supplementation in Patients With Type 2 Diabetes: The Vitamin D for Established Type 2 Diabetes (DDM2) Study.

Publications

Vitamin D Supplementation in Patients With Type 2 Diabetes: The Vitamin D for Established Type 2 Diabetes (DDM2) Study.

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